Polymer-Coated Nanoarchitectonics of Titanium Dioxide Nanoparticles with Enhanced Antimicrobial Activity: Mechanistic...

While surface modifications are widely pursued to improve antimicrobial performance of photocatalytic nanoparticles (NPs), the particle-membrane interactions responsible for these effects remain underexplored. We address this gap by investigating the influence of coating TiO₂ NPs with the cationic polymer poly-(2-(dimethylamino)-ethyl methacrylate) methyl chloride quaternary salt (qPDMAEMA). In contrast to bare TiO₂, the coated NPs adsorb extensively to negatively charged bacteria and bacteria-like membranes, boosting membrane permeabilization upon UV illumination due to formation of reactive oxygen species (ROS). The qPDMAEMA coating was demonstrated not to interfere with ROS formation and to withstand UV illumination over time-scales sufficient for membrane binding and disruption. Such effects were highly localized near membrane-bound NPs, consistent with the short diffusion lengths of ROS (≈10 nm for hydroxyl radicals) and the formation of oxidative membrane 'hot-spots' in the corresponding vicinity of membrane regions where preferential (localized) NP binding occurs. Such preferential localization is demonstrated to occur at poles and nodes of Escherichia coli bacteria. Hypothesizing this to be driven by colocalization with anionic cardiolipin, studies with giant vesicles containing cardiolipin either uniformly distributed or present in segregated domains showed that the polymer-coated TiO₂ NPs preferentially bind to cardiolipin-rich regions of the membrane. Together, these results expand on conventional studies of NP interactions with bacteria and bacteria-like membranes and demonstrate that localized interactions must be considered in studies of bacterial membrane interactions of photocatalytic NPs.